Liver Cancer Cells Uptake Labile Iron via L-type Calcium Channel to Facilitate the Cancer Cell Proliferation.

Herein, we studied the effect of labile iron (ferric chloride) on the progression of liver cancer cells (HepG2.2.15). The iron was found to induce cell proliferation, growth, and migration in both traditional two-dimensional (2D) and three-dimensional cell (3D) culture models. Biophysical and cell cycle determinations also showed the change in functional cellular biophysical features (cell morphology) and cell cycle kinetic during cancer cell growth induced by the labile iron. According to immunofluorescence and the iron uptake inhibition studies, L-type calcium channel was found to plays a role in the iron uptake in the liver cancer cells. This report gives new insights into iron-mediated cancer cell growth and will pave the new way to diagnosis and treatment of liver cancer.

Ferric-Tannic Nanoparticles Increase Neuronal Cellular Clearance.

Targeting cellular clearance function in brain cells provides new opportunities for the prevention of dementia by clearance of potentially dangerous molecules. Herein, we present a new approach to enhancing neuroactive and neuroprotective activities in a neuronal cell line using ferric-tannic nanoparticles (FTs). Major biological functions mediated by FTs were clearly found to promote neuronal tube growth through the activation of axon guidance pathways. A number of neuronal tubes were found to increase under stimulation of amyloid beta-peptides, oxidative stress, and serum deprivation. The neuronal tubes generated play a role in clearing debris and amyloid beta-peptides. Another key function in cellular clearance mediated by FTs was their capability of inducing autophagy with the activation of lysosomes. Therefore, FTs are a promising new strategy for brain cell protection through the activation of the cellular clearance function. Hopefully, our findings will pave the way for the development of new methods for the prevention and therapy of dementia.

Tannic acid (TA): A molecular tool for chelating and imaging labile iron.

This report presents the potential utilization of tannic acid (TA) as a natural iron chelator. TA is capable of binding with small ferric complexes without competitive binding with endogenous iron-containing molecules such as ferritin and transferrin. It was observed that the extracellular iron binding of TA resulted in the formation of self-assembled Fe3+-TA complexes, which were then taken up by HepG2 cells via phagocytosis pathway with autophagy-inducing properties. Obviously, TA was found to inhibit iron-induced HepG2 cell growth. However, cellular interactions and biological responses to the treatment were found to depend on availability of iron. Based on the results of the iron efflux experiment, it can be stated that TA has the capability to mobilize iron from cells in the form of assembled Fe3+-TA complexes. Interestingly, TA-mediated cellular iron influx and efflux were successfully monitored via MRI. The results of this study suggest that TA can be used as a molecular tool for chelating and imaging labile iron. This might be a promising approach for prevention and treatment of iron-associated cancer or other iron overload disorders.

Deferoxamine-conjugated AgInS2 nanoparticles as new nanodrug for synergistic therapy for hepatocellular carcinoma.

Herein, a new nanodrug that exhibits multi-therapeutic modalities for synergistic treatment of hepatocellular carcinoma is reported. The nanodrug is composed of carboxymethyl cellulose modified silver indium sulfide nanoparticle (CMC-AgInS2 NP, served as a source of reactive oxygen species) covalently linked with deferoxamine (DFO, served as iron chelating agent). The DFO/CMC-AgInS2 nanodrug was taken up by the HepG2 cell and accumulated within the cytosol as well as the nucleus, leading to induction of cell arrest in the G2/M phase and subsequent apoptosis cell death. Compared to DFO, the DFO/CMC-AgInS2 nanodrug demonstrated better anti-proliferative activity against the HepG2 cell. As they were cultured in a medium supplemented with ferric ions, the HepG2 cells were induced to grow faster as compared to the cells without the addition of ferric ions. Fortunately, our nanodrug was found to inhibit the cell growth induced by ferric ions. Our results indicate that the nanodrug has synergistic effect for treatment of HepG2 cells via the intrinsic therapeutic property of CMC-AgInS2 NP and the iron chelating capability of DFO.